Low Bone Mass, Postmenopausal Osteoporosis
Conditions
Keywords
TST002, bone mineral density, postmenopausal osteoporosis, low bone mass, sclerostin, monoclonal antibody, DXA
Brief summary
This is a randomized, double-blind, placebo- and active-controlled Phase II study evaluating the efficacy and safety of TST002 injection (a humanized monoclonal antibody) in postmenopausal women with osteoporosis or low bone mass, aged 45-80 years. Approximately 110 participants will be randomized 1:1:1:1:1 (stratified by baseline BMD T-score) to one of five arms: TST002 400 mg every 8 weeks (Q8W), TST002 800 mg Q8W, TST002 1200 mg every 12 weeks (Q12W), placebo, or open-label denosumab 60 mg subcutaneously every 24 weeks. The study includes a screening period (Day -28 to Day -1), a main study period (Week 0-24), and an extension period (Week 25-52), with all participants followed through Week 52 (Day 365). The primary objective is to evaluate the effect of repeated IV TST002 infusions on lumbar spine bone mineral density (BMD). Secondary objectives include characterization of pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability.
Detailed description
Primary Purpose: Efficacy and safety evaluation of TST002 in postmenopausal osteoporosis and low bone mass. Design: 5-arm, randomized, double-blind (denosumab arm open-label), placebo- and active-comparator (denosumab)-controlled, parallel-group study with stratified block randomization by screening BMD T-score (Stratum 1: T-score ≥ -2.00; Stratum 2: T-score \< -2.00 at all sites). Enrollment capped at \<20% Stratum 1 participants per arm. All participants receive daily calcium (600-1200 mg elemental) and vitamin D (725-1450 IU) supplementation from screening through study end, with an optional vitamin D loading dose for those with baseline 25(OH)D 20-40 ng/mL. Unblinding: Primary analysis after all participants complete Week 24 is performed by an unblinded CRO team; investigators, participants, and the CRO study team (except for the open-label denosumab arm) remain blinded until final study unblinding
Interventions
DRUGDenosumab
Active comparator
DRUGPlacebo
Vehicle Placebo
Sponsors
Transcenta Therapeutics (Hangzhou) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Double-blind (Participant, Investigator) TST002 doses or placebo; denosumab arm open-label
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntary signed informed consent; able to walk freely; willing/able to complete all study procedures. 2. BMI 18.0-30.0 kg/m² (inclusive); body weight ≥45 kg. 3. Postmenopausal women aged 45-80 years (inclusive) at screening, postmenopausal ≥2 years (≥12 consecutive months without spontaneous vaginal bleeding/spotting). 4. BMD T-score \<-2.00 at lumbar spine (L1-L4 total), total hip, or femoral neck at screening; OR history of fragility fracture with T-score \<-1.00 at one of these sites (central imaging read). 5. At least 2 contiguous evaluable vertebrae (L1-L4) and at least one evaluable hip for DXA assessment. 6. No disease, per investigator history/exam/workup, likely to significantly affect the study or increase health risk (documented exceptions permitted with justification).
Exclusion criteria
1. BMD T-score ≤-3.50 at lumbar spine, total hip, or femoral neck at screening. 2. Prior hip fracture. 3. ≥2 vertebral fractures on screening lateral spine X-ray (investigator-assessed). 4. Known skeletal, endocrine, or rheumatic disease that could confound results (e.g., Paget's disease, osteomalacia, osteopetrosis, osteogenesis imperfecta, sclerosteosis, rheumatoid arthritis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, uncontrolled thyroid disease, hyper-/hypoparathyroidism, or CN VIII compression hearing loss). 5. Prior osteoporosis therapy (incl. trial participation) within protocol-specified washout windows (IV bisphosphonates, oral bisphosphonates, denosumab/cathepsin K inhibitors, tibolone/cinacalcet/calcitonin, teriparatide/PTH analogs, systemic estrogen/SERMs, strontium ranelate/fluoride, hormonal castration therapy, systemic glucocorticoids ≥5 mg/day prednisone-equivalent for \>14 days) - see protocol for exact windows per agent. 6. History of TMJ disorder, TMJ osteonecrosis, or atypical fracture. 7. Hypercalcemia or hypocalcemia (albumin-corrected) at screening. 8. Serum 25(OH)D \<20 ng/mL at screening. 9. History of MI, or serious cardiac disease (CAD, NYHA class II-IV heart failure) within 6 months before screening. 10. History of stroke (cerebral infarction, ischemic or hemorrhagic). 11. ALT/AST \>3× ULN; ALP \>2.5× ULN; total bilirubin or creatinine \>1.5× ULN at screening. 12. Multiple myeloma, primary/metastatic bone malignancy, or history of skeletal radiotherapy. 13. Malignancy within 5 years before screening (except cured skin squamous/basal cell carcinoma or documented cured in situ cervical cancer, no recurrence ≥3 months before dosing). 14. Known hypersensitivity to study drug. 15. History of solid organ or bone marrow transplant. 16. Positive HIV, syphilis, HCV antibody, or HBsAg at screening; or HBcAb-positive with detectable HBV DNA. 17. Active tuberculosis within 6 months before screening. 18. Participation in another clinical trial within 30 days or 5 half-lives of the investigational product (whichever longer) before screening. 19. Any other condition the investigator judges unsuitable for participation, a safety risk, or interfering with study assessments/completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline in lumbar spine Bone Mineral Density (BMD) | Baseline to Week 24 | Lumbar spine (L1-L4) bone mineral density, central imaging read (DXA) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline in lumbar spine Bone Mineral Density (BMD) | Weeks 12 and 52 | Central imaging read (DXA) |
| Percent change from baseline in total hip Bone Mineral Density (BMD) | Weeks 12, 24, and 52 | Central imaging read (DXA) |
| Percent change from baseline in femoral neck Bone Mineral Density (BMD) | Weeks 12, 24 and 52 | Central imaging DXA |
| TST002 plasma concentration | Up to 52 weeks | Plasma concentrations at each dosing timepoint |
| Percent change from baseline in bone turnover markers | Up to 52 weeks | P1NP, β-CTX, OC, BSAP, TRACP-5b, and total sclerostin |
| Anti-drug antibody (ADA) positivity rate | Up to 52 weeks | Immunogenicity - proportion positive and time to first positive |
| Incidence of adverse events | Up to 52 weeks | AEs, vital signs, physical exam, and clinically significant lab abnormalities (CTCAE v6.0 graded) |
| TST002 Concentration-time | Up to 52 weeks | Area under curve (AUC) |
| TST002 Peak Plasma Concentration | Up to 52 weeks | Cmax |
| TST002 Trough Concentrations | Up to 52 weeks | Ctrough |
| TST002 Half-life | Up to 52 weeks | T1/2 |
| TST002 Systemic Clearance | Up to 52 weeks | CL |
| TST002 Volume of Distribution | Out to 52 weeks | Vd |
| TST002 Effects on total Sclerostin | Up to 52 weeks | Pharmacodynamic effects |
| TST002 Effects on total P1NP | Up to 52 weeks | Pharmacodynamic effects of Serum N-terminal propeptide of procollagen type 1 |
| TST002 Effects on total B-CTX | Out to 52 weeks | Pharmacodynamic effects of Beta-C-terminal telopeptide |
| TST002 Effects on total OC | Out to 52 weeks | Pharmacodynamic effects of osteocalcin |
| TST002 Effects on total BSAP | Up to 52 weeks | Pharmacodynamic effects of Bone-specific alkaline phosphatase |
| TST002 Effects on total TRACP-5b | Up to 52 weeks | Pharmacodynamic effects of Tartrate-Resistant Acid Phosphatase 5b |
Contacts
CONTACTVicky Zhong
Outcome results
None listed